Fungicidal mixtures based on imidazole derivatives

ABSTRACT

Disclosed are fungicidal mixtures containing a synergistically effective amount of A) a triazolopyrimidine of formula I, and B) imidazole derivatives of formula II, wherein X 1  and X 2  represent halogen and phenyl which can be substituted by halogen or alkyl, or X 1  and X 2  form a difluoromethylendioxyphenyl group along with the bridging C═C double bond, X 3  represents cyano or halogen, and X 4  represents dialkylamino or isoxazol-4yl that can carry two alkyl radicals. The invention also relates to methods for controlling destructive fungi by means of mixtures of compounds I and II, agents containing said mixtures, and the use of compounds I and II for producing such mixtures.

This application is a 371 of PCT/EP03/12770, filed on 11/14/2003.

The present invention relates to fungicidal mixtures, comprising

A) the triazolopyrimidine of the formula I

B) imidazole derivatives of the formula II

-   -   where X¹ and X² are halogen and phenyl which may be substituted        by halogen or C₁-C₄-alkyl or    -   X¹ and X² together with the bridging C═C double bond form a        3,4-difluoromethylendioxyphenyl group;    -   X³ is cyano or halogen, and    -   X⁴ is di-(C₁-C₄-alkyl)amino or isoxazol-4-yl which may carry two        C₁-C₄-alkyl radicals,        in a synergistically effective amount.

Moreover, the invention relates to methods for controllingphytopathogenic harmful fungi using mixtures of the compounds I and II,to compositions comprising these mixtures and to the use of thecompounds I and II for preparing such mixtures.

The compound of the formula1,5-chloro-7-(4-methyl-pipiridin-1-yl)-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,its preparation and its action against harmful fungi are known from theliterature (WO 98/46607).

Mixtures of triazolopyrimidines of the formula I with other activecompounds are known from EP-A 988 790 and U.S. Pat. No. 6,268,371.

Also known are the imidazole derivatives of the formula II, theirpreparation and their action against harmful fungi (EP-A 298 196, WO97/06171).

Mixtures of the imidazole derivatives of the formula II with otheractive compounds are known from WO 98/48628 and WO 00/30440.

To reduce the risk of selection of resistant fungus strains, it isnowadays customary to use mixtures of different active compounds forcontrolling harmful fungi. By combining active compounds havingdifferent mechanisms of action, it is possible to ensure successfulcontrol over a relatively long period of time.

It is an object of the present invention to provide further particularlyeffective mixtures for controlling harmful fungi and in particular forcertain indications.

With a view to effective resistance management and reducing theapplication rates and to improving the activity spectrum of the knowncompounds I and II, it was an object of the present invention to providemixtures which, with the total amount of active compounds applied beingreduced, have improved action against harmful fungi (synergisticmixtures).

We have found that this object is achieved by the mixtures defined atthe outset. Moreover, it has been found that simultaneous, that is jointor separate, application of the compounds I and the compounds II orsuccessive application of the compounds I and the compounds II allowsbetter control of harmful fungi than is possible with the individualcompounds alone.

The mixtures according to the invention have synergistic action and aretherefore particularly suitable for controlling harmful fungi and inparticular powdery and downy mildew fungi in cereals, vegetables, fruit,ornamental plants and grapevines.

The mixtures according to the invention preferably comprise, as activecomponents, the compound of the formula I and a compound of the formulaII.

Preference is given to compounds of the formula II in which X¹ ishalogen, in particular chlorine, and X² is tolyl, in particular p-tolyl.

Preference is likewise given to compounds of the formula II, in which X⁴is dimethylamino.

In addition, particular preference is given to the compound of theformula IIa (common name: cyazofamid). This compound is known from EP-A298 196.

Preference is furthermore given to compounds of the formula II in whichX¹ and X² together with the bridging C═C double bond form a3,4-difluoromethylendioxyphenyl group.

In addition, preference is given to compounds of the formula II in whichX⁴ is 3,5-dimethylisoxazol-4-yl.

Particular preference is given to compounds of the formula IIb in whichY is halogen.

Halogen denotes fluorine, chlorine, bromine and iodine. Particularpreference is given to compounds of the formula IIb in which Y isbromine (IIb-1) or chlorine (IIb-2).

For use in mixtures with the triazolopyrimidine of the formula I,preference is given to compound IIa.

Owing to the basic character of their nitrogen atoms, the compounds Iand II are capable of forming salts or adducts with inorganic or organicacids or with metal ions.

Examples of inorganic acids are hydrohalic acids such as hydrogenfluoride, hydrogen chloride, hydrogen bromide and hydrogen iodide,sulfuric acid, phosphoric acid and nitric acid.

Suitable organic acids are, for example, formic acid, carbonic acid andalkanoic acids, such as acetic acid, trifluoroacetic acid,trichloroacetic acid and propionic acid, and also glycolic acid,thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid,cinnamic acid, oxalic acid, alkylsulfonic acids (sulfonic acids havingstraight-chain or branched alkyl radicals of 1 to 20 carbon atoms),arylsulfonic acids or -disulfonic acids (aromatic radicals, such asphenyl and naphthyl, which carry one or two sulfonic acid groups),alkylphosphonic acids (phosphonic acids having straight-chain orbranched alkyl radicals of 1 to 20 carbon atoms), arylphosphonic acidsor -diphosphonic acids (aromatic radicals, such as phenyl and naphthyl,which carry one or two phosphonic acid radicals), where the alkyl andaryl radicals may carry further substituents, for examplep-toluenesulfonic acid, salicylic acid, p-aminosalicylic acid,2-phenoxybenzoic acid, 2-acetoxybenzoic acid, etc.

Suitable metal ions are, in particular, the ions of the elements of thefirst to eighth subgroup, in particular chromium, manganese, iron,cobalt, nickel, copper, zinc, and furthermore of the second main group,in particular calcium and magnesium, and of the third and fourth maingroup, in particular aluminum, tin and lead. The metals can exist in thevarious valencies which they can assume.

The ratio of the compounds I and II can be varied within wide ranges;preferably, the active compounds are employed in a weight ratio in therange from 50:1 to 1:50, preferably from 20:1 to 1:20, in particularfrom 10:1 to 1:10.

When preparing the mixtures, it is preferred to employ the pure activecompounds I and II, to which further active compounds against harmfulfungi or other pests, such as insects, arachnids or nematodes, or elseherbicidal or growth-regulating active ingredients or fertilizers can beadded.

The mixtures of the compounds I and II, or the compounds I and II usedsimultaneously, together or separately, exhibit outstanding activityagainst a wide range of phytopathogenic fungi, in articular from theclasses of the Ascomycetes, Basidiomycetes, Phycomycetes andDeuteromycetes. Some of them act systemically and can therefore also beemployed as foliar- and soil-acting fungicides.

They are especially important for controlling a large number of fungi ina variety of crop plants, such as cotton, vegetable species (for examplecucumbers, beans, tomatoes, potatoes and cucurbits), barley, grass,oats, bananas, coffee, corn, fruit species, rice, rye, soybean,grapevine, wheat, ornamentals, sugar cane, and a multiplicity of seeds.

They are particularly suitable for controlling the followingphytopathogenic fungi: Blumeria graminis (powdery mildew) in cereals,Erysiphe cichoracearum and Sphaerotheca fuliginea in cucurbits,Podosphaera leucotricha in apples, Uncinula necator in grapevines,Puccinia species in cereals, Rhizoctonia species in cotton, rice andlawns, Ustilago species in cereals and sugar cane, Venturia inaequalisin apples, Bipolaris and Drechslera species in cereals, rice and lawns,Septoria nodorum in wheat, Botrytis cinera in strawberries, vegetables,ornamentals and grapevines, Mycosphaerella species in bananas,groundnuts and cereals, Pseudocercosporella herpotrichoides in wheat andbarley, Pyricularia oryzae in rice, Phytophthora infestans in potatoesand tomatoes, Pseudoperonospora species in cucurbits and hops,Plasmopara viticola in grapevines, Alternaria species in vegetables andfruit and also Fusarium and Verticillium species.

Moreover, they can be used in the protection of materials (for examplethe protection of wood), for example against Paecilomyces variotii.

The compounds I and II can be applied simultaneously, that is eithertogether or separately, or in succession, the sequence, in the case ofseparate application, generally not having any effect on the result ofthe control measures.

Depending on the kind of effect desired, the application rates of themixtures according to the invention are, in particular in agriculturalcrop areas, from 0.01 to 2 kg/ha, preferably from 0.05 to 1.5 kg/ha, inparticular from 0.05 to 0.75 kg/ha.

The application rates of the compounds I are from 10 g/ha to 1 000kg/ha, preferably from 20 to 750 kg/ha, in particular from 20 to 500kg/ha.

Correspondingly, in the case of the compounds II, the application ratesare from 5 g/ha to 500 g/ha, preferably from 50 to 500 g/ha, inparticular from 50 to 200 g/ha.

For seed treatment, the application rates of the mixture are generallyfrom 0.001 to 1 g/kg of seed, preferably from 0.01 to 0.5 g/kg, inparticular from 0.01 to 0.1 g/kg.

If phytopathogenic harmful fungi are to be controlled, the separate orjoint application of the compounds I and II or of the mixtures of thecompounds I and II is effected by spraying or dusting the seeds, theplants or the soils before or after sowing of the plants, or before orafter plant emergence.

The mixtures according to the invention, or the compounds I and II, canbe converted into the customary formulations, for example solutions,emulsions, suspensions, dusts, powders, pastes and granules. The useform depends on the respective intended purpose; in each case, it shouldensure a fine and uniform distribution of the mixture according to theinvention.

The formulations are prepared in a known manner, e.g. by extending theactive compound with solvents and/or carriers, if desired usingemulsifiers and dispersants. Suitable solvents/auxiliaries for thispurpose are essentially:

-   -   water, aromatic solvents (for example Solvesso products,        xylene), paraffins (for example mineral oil fractions), alcohols        (for example methanol, butanol, pentanol, benzyl alcohol),        ketones (for example cyclohexanone, gamma-butryolactone),        pyrrolidones (NMP, NOP), acetates (glycol diacetate), glycols,        fatty acid dimethylamides, fatty acids and fatty acid esters. In        principle, solvent mixtures may also be used,    -   carriers such as ground natural minerals (for example kaolins,        clays, talc, chalk) and ground synthetic minerals (for example        finely divided silica, silicates); emulsifiers such as nonionic        and anionic emulsifiers (for example polyoxyethylene fatty        alcohol ethers, alkylsulfonates and arylsulfonates) and        dispersants such as lignosulfite waste liquors and        methylcellulose.

Suitable surfactants are the alkali metal salts, alkaline earth metalsalts and ammonium salts of lignosulfonic acid, naphthalenesulfonicacid, phenolsulfonic acid, dibutylnaphthalenesulfonic acid,alkylarylsulfonates, alkyl sulfates, alkylsulfonates, fatty alcoholsulfates, fatty acids and sulfated fatty alcohol glycol ethers,furthermore condensates of sulfonated naphthalene and naphthalenederivatives with formaldehyde, condensates of naphthalene or ofnaphthalenesulfonic acid with phenol and formaldehyde, polyoxyethyleneoctylphenyl ether, ethoxylated isooctylphenol, octylphenol, nonylphenol,alkylphenyl polyglycol ethers, tributylphenyl polyglycol ether,tristerylphenyl polyglycol ether, alkylaryl polyether alcohols,alcohol/- and fatty alcohol/ethylene oxide condensates, ethoxylatedcastor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene,lauryl alcohol polyglycol ether acetal, sorbitol esters, lignosulfitewaste liquors and methylcellulose.

Substances which are suitable for the preparation of directly sprayablesolutions, emulsions, pastes or oil dispersions are mineral oilfractions of medium to high boiling point, such as kerosene or dieseloil, furthermore coal tar oils and oils of vegetable or animal origin,aliphatic, cyclic and aromatic hydrocarbons, for example toluene,xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes or theirderivatives, methanol, ethanol, propanol, butanol, cyclohexanol,cyclohexanone, isophorone, highly polar solvents, for example dimethylsulfoxide, N-methylpyrrolidone or water.

Powders, compositions for broadcasting and dusts can be prepared bymixing or jointly grinding the active substances with a solid carrier.

Granules, for example coated granules, impregnated granules andhomogeneous granules, can be prepared by binding the active compounds tosolid carriers. Examples of solid carriers are mineral earths such assilica gels, silicates, talc, kaolin, attaclay, limestone, lime, chalk,bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate,magnesium sulfate, magnesium oxide, ground synthetic minerals,fertilizers, such as, for example, ammonium sulfate, ammonium phosphate,ammonium nitrate, ureas, and products of vegetable origin, such ascereal meal, tree bark meal, wood meal and nutshell meal, cellulosepowders and other solid carriers.

The formulations generally comprise from 0.01 to 95% by weight,preferably from 0.1 to 90% by weight, of the active compounds. Theactive compounds are employed in a purity of from 90% to 100%,preferably from 95% to 100% (according to NMR spectrum).

The following are examples of formulations:

1. Products for dilution with water

A) Water-Soluble Concentrates (SL)

-   -   10 parts by weight of the active compounds are dissolved in        water or in a water-soluble solvent. As an alternative, wetters        or other auxiliaries are added. The active compound dissolves        upon dilution with water.        B) Dispersible Concentrates (DC)    -   20 parts by weight of the active compounds are dissolved in        cyclohexanone with addition of a dispersant, for example        polyvinylpyrrolidone. Dilution with water gives a dispersion.        C) Emulsifiable Concentrates (EC)    -   15 parts by weight of the active compounds are dissolved in        xylene with addition of calcium dodecylbenzenesulfonate and        castor oil ethoxylate (in each case 5%). Dilution with water        gives an emulsion.        D) Emulsions (EW, EO)    -   40 parts by weight of the active compounds are dissolved in        xylene with addition of calcium dodecylbenzenesulfonate and        castor oil ethoxylate (in each case 5%). This mixture is        introduced into water by means of an emulsifier (Ultraturax) and        made into a homogeneous emulsion. Dilution with water gives an        emulsion.        E) Suspensions (SC, OD)    -   In an agitated ball mill, 20 parts by weight of the active        compounds are comminuted with addition of dispersant, wetters        and water or an organic solvent to give a fine active compound        suspension. Dilution with water gives a stable suspension of the        active compound.        F) Water-Dispersible Granules and Water-Soluble Granules (WG,        SG)    -   50 parts by weight of the active compounds are ground finely        with addition of dispersants and wetters and made into        water-dispersible or water-soluble granules by means of        technical appliances (for example extrusion, spray tower,        fluidized bed). Dilution with water gives a stable dispersion or        solution of the active compound.        G) Water-Dispersible Powders and Water-Soluble Powders (WP, SP)    -   75 parts by weight of the active compounds are ground in a        rotor-stator mill with addition of dispersants, wetters and        silica gel. Dilution with water gives a stable dispersion or        solution of the active compound.        2. Products to be Applied Undiluted        H) Dustable Powders (DP)    -   5 parts by weight of the active compounds are ground finely and        mixed intimately with 95% of finely divided kaolin. This gives a        dustable product.        I) Granules (GR, FG, GG, MG)    -   0.5 part by weight of the active compounds is ground finely and        associated with 95.5% carriers. Current methods are extrusion,        spray-drying or fluidized bed. This gives granules to be applied        undiluted.        J) ULV Solutions (UL)    -   10 parts by weight of the active compounds are dissolved in an        organic solvent, for example xylene. This gives a product to be        applied undiluted.

The active compounds can be used as such, in the form of theirformulations or the use forms prepared therefrom, for example in theform of directly sprayable solutions, powders, suspensions ordispersions, emulsions, oil dispersions, pastes, dust compositions,compositions for broadcasting, or granules, by means of spraying,atomizing, dusting, broadcasting or pouring. The use forms dependentirely on the intended purposes; it is intended to ensure in each casethe finest possible distribution of the active compounds according tothe invention.

Aqueous use forms can be prepared from emulsion concentrates, pastes orwettable powders (sprayable powders, oil dispersions) by adding water.To prepare emulsions, pastes or oil dispersions, the substances, as suchor dissolved in an oil or solvent, can be homogenized in water by meansof a wetter, tackifier, dispersant or emulsifier. Alternatively, it ispossible to prepare concentrates suitable for dilution with watercomposed of active substance, wetter, tackifier, dispersant oremulsifier and, if appropriate, solvent or oil.

The active compound concentrations in the ready-to-use preparations canbe varied within relatively wide ranges. In general, they are from0.0001 to 10%, preferably from 0.01 to 1%.

The active compounds may also be used successfully in theultra-low-volume process (ULV), where it is possible to applyformulations comprising over 95% by weight of active compound, or evento apply the active compound without additives.

Oils of various type, wetters, adjuvants, herbicides, fungicides, otherpesticides, or bactericides may be added to the active compounds, ifappropriate just immediately prior to use (tank mix). These agents canbe admixed with the agents according to the invention in a weight ratioof 1:10 to 10:1.

USE EXAMPLES

The synergistic activity of the mixtures according to the invention canbe demonstrated by the following experiments:

The active compounds, separately or together, were prepared as a stocksolution with 0.25% by weight of active compound in acetone or DMSO. 1%by weight of the emulsifier Uniperol® EL (wetting agent havingemulsifying and dispersing action based on ethoxylated alkylphenols) wasadded to this solution, and the solution was diluted with water to thedesired concentration.

Evaluation is carried out by determining the infected leaf areas as apercentage. These percentages are converted into efficacies. Theefficacy (W) is calculated as follows using Abbot's formula:W=(1−α/β)·100

α corresponds to the fungal infection of the treated plants in % and

β corresponds to the fungal infection of the untreated (control) plantsin %

An efficacy of 0 means that the infection level of the treated plantscorresponds to that of the untreated control plants; an efficacy of 100means that the treated plants were not infected. The expected efficaciesof the mixtures of the active compounds are determined using Colby'sformula [R. S. Colby, Weeds 15, 20-22 (1967)] and compared with theobserved efficacies.Colby's formula: E=x+y−x·y/100

E expected efficacy, expressed as a % of the untreated control, whenusing the mixture of the active compounds A and B at the concentrationsa and b

x efficacy, expressed as a % of the untreated control, when using activecompound A at a concentration a

y efficacy, expressed as a % of the untreated control, when using activecompound B at a concentration b

Example 1 Activity Against peronospora of Vines Caused by Plasmoparaviticola

Leaves of potted vines of the cultivar “Müller-Thurgau” were sprayed torunoff point with an aqueous suspension having the concentration ofactive compounds stated below. The next day, the undersides of theleaves were inoculated with an aqueous zoospore suspension of Plasmoparaviticola. The vines were then initially placed in awater-vapor-saturated chamber at 24° C. for 48 hours and then in agreenhouse at 20-30° C. for 5 days. After this period of time, theplants were again placed in a moist chamber for 16 hours to promotesporangiophore eruption. The extent to which the infection had developedon the undersides of the leaves was then determined visually.

TABLE A individual active compounds Concentration of active compound inEfficacy in % of Experiment Active the spray liquor the untreated No.compound [ppm] control 1 Control (88% infection) 0 (untreated) 2 I 7.532 3.75 9 3 IIa 6 83 (cyazofamid) 3 72 4 IIb-1 6 9 3 9 0.75 0 0.375 0

TABLE B mixtures according to the invention Mixture of active compoundsExperiment Concentration Observed Calculated No. Mixing ratio efficacyefficacy*) 5 I + IIa 100 88 7.5 + 6 ppm 1.25:1 6 I + IIa 97 74 3.75 + 3ppm 1.25:1 7 I + IIa 97 85 3.75 + 6 ppm 1:1.6 8 I + IIb-1 66 32 7.5 +0.75 ppm 10:1 9 I + IIb-1 32 9 3.75 + 0.375 ppm 10:1 10 I + IIb-1 77 387.5 + 6 ppm 1.25:1 11 I + IIb-1 66 17 3.75 + 3 ppm 1.25:1 12 I + IIb-155 17 3.75 + 6 ppm 1:1.6 *)efficacy calculated using Colby's formula

Example 2 Activity Against Late Blight of Tomato Caused by Phytophthorainfestans

Leaves of potted plants of the cultivar “Groβe Fleischtomate St. Pierre”were sprayed to runoff point with an aqueous suspension having theconcentration of active compound stated below. The next day, the leaveswere infected with a cold aqueous zoospore suspension of Phytophthorainfestans having a density of 0.25×10⁶ spores/ml. The plants were thenplaced in a water-vapor-saturated chamber at 18-20° C. After 6 days, thelate blight on the untreated, but infected control plants had developedto such an extent that the infection could be determined visually in %.

TABLE C individual active compounds Concentration of active compound inEfficacy in % of Experiment Active the spray liquid the untreated No.compound [ppm] control 13 Control (90% infection) 0 (untreated) 14 I 3033 15 0 7.5 0 3.75 0 15 IIa 6 89 (cyazofamid) 3 78 1.5 67 0.75 56 16IIb-1 6 83 3 44 0.75 0 0.375 0

TABLE D combinations according to the invention Mixture of activecompounds Experiment Concentration Observed Calculated No. Mixing ratioefficacy efficacy*) 17 I + IIa 99 85 30 + 3 ppm 10:1 18 I + IIa 94 6715 + 1.5 ppm 10:1 19 I + IIa 99 78 3.75 + 3 ppm 1.25:1 20 I + IIa 100 893.75 + 6 ppm 1:1.6 21 I + IIb-1 44 0 7.5 + 0.75 ppm 10:1 22 I + IIb-1 560 3.75 + 0.375 ppm 10:1 23 I + IIb-1 61 44 3.75 + 3 ppm 1.25:1 24 I +IIb-1 94 83 3.75 + 6 ppm 1:1.6 *)efficacy calculated using Colby'sformula

The test results show that for all mixing ratios the observed efficacyof the mixtures according to the invention is considerably higher thanthat predicted using Colby's formula.

1. A fungicidal mixture, comprising A) the triazolopyrimidine of theformula I

and B) an imidazole derivative of the formula II

where X¹ and X² are halogen and phenyl, respectively, wherein phenyl maybe substituted by halogen or C₁-C₄-alkyl or X¹ and X² together with thebridging C═C double bond form a 3,4-difluoromethylendioxyphenyl group;X³ is cyano or halogen, and X⁴ is di-(C₁-C₄-alkyl)amino or isoxazol-4-ylwhich may carry two C₁-C₄-alkyl radicals, in a synergistically effectiveamount.
 2. A fungicidal mixture as claimed in claim 1, comprising, asthe imidazole derivative, the compound IIa


3. A fungicidal mixture as claimed in claim 1, comprising, as theimidazole derivative, a compound of the formula IIb,

wherein Y is halogen.
 4. A fungicidal mixture as claimed in any one ofclaims 1 to 3, wherein the weight ratio of the triazolopyrimidine of theformula I to the imidazole derivative of the formula II is from 50:1 to1:50.
 5. A fungicidal composition, comprising the fungicidal mixture asclaimed in claim 1 and a solid or liquid carrier.
 6. A method forcontrolling phytopathogenic harmful fungi, which comprises treating theharmful fungi, their habitat or the plants, seeds, soils, areas,materials or spaces to be kept free from them with thetriazolopyrimidine of the formula I as set forth in claim 1 and animidazole derivative of the formula II as set forth in claim
 1. 7. Amethod as claimed in claim 6, wherein the triazolopyrimidine of theformula I and an imidazole derivative of the formula II are appliedsimultaneously, that is either together or separately, or in succession.8. A method as claimed in claim 6, wherein the triazolopyrimidine of theformula I is applied in an amount of from 0.01 to 2.5 kg/ha.
 9. A methodas claimed in claim 6, wherein the imidazole derivative of the formulaII is applied in an amount of from 5 g/ha to 500 g/ha.
 10. A fungicidalmixture as claimed in any one of claims 1 to 3, wherein the weight ratioof the triazolopyrimidine of the formula I to the imidazole derivativeof the formula II is from 20:1 to 1:20.
 11. A fungicidal mixture asclaimed in any one of claims 1 to 3, wherein the weight ratio of thetriazolopyrimidine of the formula I to the imidazole derivative of theformula II is from 10:1 to 1:10.